INTRACEREBROVENTRICULAR INFUSION OF NERVE GROWTH-FACTOR IN 3 PATIENTSWITH ALZHEIMERS-DISEASE

Nerve growth factor (NGF) is important for the survival and maintenanc e of central cholinergic neurons, a signalling system impaired in Alzh eimer's disease, We have treated 3 patients with Alzheimer's disease w ith a total of 6.6 mg NGF administered continuously into the lateral c erebral ventricle for 3 months in the first 2 patients and a total of 0.55 mg for 3 shorter periods in the third patient, The patients were extensively evaluated with clinical, neuropsychological, neurophysiolo gical and neuroradiological techniques, Three months after the NGF tre atment ended, a significant increase in nicotine binding was found in several brain areas in the first 2 patients and in the hippocampus in the third patient as studied by positron emission tomography. A clear cognitive amelioration could not be demonstrated, although a few neuro psychology tests showed slight improvements, The amount of slow-wave c ortical activity as studied by electroencephalography was reduced in t he first 2 patients. Two negative side effects occurred with NGF treat ment: first, a dull, constant back pain was observed in all 3 patients , which in 1 patient was aggravated by axial loading resulting in shar p, shooting pain of short duration, When stopping the NGF infusion, th e pain disappeared within a couple of days, Reducing the dose of NGF l essened the pain. Secondly, a marked weight reduction during the infus ion with a clear weight gain after ending the infusion was seen in the first 2 patients. We conclude from this limited trial that, while lon g-term intracerebroventricular NGF administration may cause certain po tentially beneficial effects, the intraventricular route of administra tion is also associated with negative side effects that appear to outw eigh the positive effects of the present protocol, Alternative routes of administration, and/or lower doses of NGF, perhaps combined with lo w doses of other neurotrophic factors, may shift this balance in favor of positive effects.